Roles of flanking sequences in the binding between unimolecular parallel-stranded G-quadruplexes and ligands

• Published in: 中国科学：技术科学英文版 2013 (3), p.731-740
• Main Author: GAI Wei YANG QianFan XIANG JunFeng SUN HongXia SHANG Qian LI Qian JIANG Wei GUAN AiJiao ZHANG Hong TANG YaLin XU GuangZhi
• Format: Article
• Language: English
• Subjects: c-myc基因; G-四链体; 侧翼序列; 单分子链; 平行链; 旁侧序列; 结合亲和力; 配体
• ISSN: 1674-7321; 1869-1900

G-quadruplexes attract more and more attention in recent years. Numerous small molecules which can induce or stabilize the for- mation of G-quadruplexes have been investigated on the purpose of anticancer drug development. As a motif existed in physio- logical condition, flanking sequences are an important part of G-quadruplexes but the study on the impact of flanking sequences on （G-quadruplex）-ligand binding is rarely reported. In this paper, the effects of flanking sequences on binding affinity between a series of unimolecular parallel-stranded G-quadruplex sequences derived from c-myc oncogene promoter （termed as c-myc G-quadruplexes） and their ligands are discussed in detail. The results showed that the flanking sequences on c-myc G-quadru- plexes play key roles in （G-quadruplex）-ligand interaction. When a c-myc G-quadruplex is bound to its ligands, the flanking se- quences might form a binding cavity above the terminal G-quartet, which could provide a suitable site for ligands to dock in. Moreover, the bases on flanking sequences could interact with ligand through π-π stacking, and finally form a sandwich-stacking mode （terminal G-quartet, ligand and bases on the flanking sequence）. This mode could stabilize the （G-quadruplex）-ligand com- plex effectively and enhance the binding affinity dramatically. However, flanking sequences are also found to exhibit steric hin- drance effect which could impede the （G-quadruplex）-ligand binding.